tbuckley/cabot-search huggingface dataset:
Unc51-like-kinase 1-mediated mitophagy prevents pathological cardiac remodelling and heart failure
Authors: Rimpy Dhingra, Lorrie A Kirshenbaum
Journal: Cardiovascular Research (2022)

This editorial refers to 'Ulk1-dependent alternative mitophagy plays a protective role during pressure overload in the heart' by J. Nah et al.,https://doi.org/10.1093/cvr/cvac003. The quintessential response of the myocardium to increased work load is heart hypertrophy. Heart hypertrophy is an adaptive response mechanism that promotes growth of the heart muscle in attempt to normalize diastolic filling pressure.1 Cardiac hypertrophy can result from an increase in peripheral resistance, valvular defects, or cardiac injury following myocardial infarction. These changes set into motion a cascade of signalling events that promote cardiac myocyte growth. The physiological increase in cardiac wall mass off-sets the increased ventricular loading conditions and maintains cardiac function according to the Laws of Laplace, reviewed in.2,3 In general, the heart is among the most metabolically active organs in the body with a high energy demand for maintaining normal cardiac functioning, which rises exponentially in response to hypertrophic growth. For this reason, cardiac myocytes rely heavily on mitochondrial oxidative metabolism as the primary adenosine triphosphate (ATP) source and is reflected by the fact that more than 30% of the cardiac myocyte volume is comprised of mitochondria. However, with the continuous loss of functional mitochondria and consequential decline in ATP, the adaptive hypertrophic response can readily transition into pathological hypertrophy resulting in heart failure.4
The epithelial-specific ER stress sensor ERN2/IRE1β enables host-microbiota crosstalk to affect colon goblet cell development
Authors: Michael J. Grey, Heidi De Luca, Doyle V. Ward, Irini A.M. Kreulen, Katlynn Bugda Gwilt, Sage E. Foley, Jay R. Thiagarajah, Beth A. McCormick, Jerrold R. Turner, Wayne I. Lencer
Journal: Journal of Clinical Investigation (2022)

Epithelial cells lining mucosal surfaces of the gastrointestinal and respiratory tracts uniquely express ERN2/IRE1β, a paralogue of the most evolutionarily conserved endoplasmic reticulum stress sensor, ERN1/IRE1α. How ERN2 functions at the host-environment interface and why a second paralogue evolved remain incompletely understood. Using conventionally raised and germ-free Ern2-/- mice, we found that ERN2 was required for microbiota-induced goblet cell maturation and mucus barrier assembly in the colon. This occurred only after colonization of the alimentary tract with normal gut microflora, which induced Ern2 expression. ERN2 acted by splicing Xbp1 mRNA to expand ER function and prevent ER stress in goblet cells. Although ERN1 can also splice Xbp1 mRNA, it did not act redundantly to ERN2 in this context. By regulating assembly of the colon mucus layer, ERN2 further shaped the composition of the gut microbiota. Mice lacking Ern2 had a dysbiotic microbial community that failed to induce goblet cell development and increased susceptibility to colitis when transferred into germ-free WT mice. These results show that ERN2 evolved at mucosal surfaces to mediate crosstalk between gut microbes and the colonic epithelium required for normal homeostasis and host defense.
Omicron subvariants escape antibodies elicited by vaccination and BA.2.2 infection
Authors: Lin Yao, Ka-Li Zhu, Xiao-Lin Jiang, Xue-Jun Wang, Bing-Dong Zhan, Hui-Xia Gao, Xing-Yi Geng, Li-Jun Duan, Er-Hei Dai, Mai-Juan Ma
Journal: The Lancet Infectious Diseases (2022)
Publisher Correction: A D2 to D1 shift in dopaminergic inputs to midbrain 5-HT neurons causes anorexia in mice
Authors: Xing Cai, Hailan Liu, Bing Feng, Meng Yu, Yang He, Hesong Liu, Chen Liang, Yongjie Yang, Longlong Tu, Nan Zhang, Lina Wang, Na Yin, Junying Han, Zili Yan, Chunmei Wang, Pingwen Xu, Qi Wu, Qingchun Tong, Yanlin He, Yong Xu
Journal: Nature Neuroscience (2022)
Identification and Management of Learner Burnout in Cardiology Fellowship Programs
Authors: Michael W. Cullen, Julie B. Damp, Victor Soukoulis, Friederike K. Keating, Islam Abudayyeh, Alex Auseon, Atif Qasim, Marty C. Tam, Paul Theriot, Gaby Weissman
Journal: Journal of the American College of Cardiology (2022)
Whole blood microRNAs capture systemic reprogramming and have diagnostic potential in patients with biliary tract cancer
Authors: Dan Høgdall, Colm J. O’Rourke, Finn O. Larsen, Shahryar Zarforoushan, Troels D. Christensen, Awaisa Ghazal, Mogens K. Boisen, Patricia Muñoz-Garrido, Julia S. Johansen, Jesper B. Andersen
Journal: Journal of Hepatology (2022)
Letters
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
The Relationship of Pain Reduction With Prevention of Knee Replacement Under Dynamic Intervention Strategies
Authors: S. Reza Jafarzadeh, Tuhina Neogi, Daniel K. White, David T. Felson
Journal: Arthritis & Rheumatology (2022)

Knee replacement (KR) rates are increasing exponentially in the US and straining insurance budgets. This study was undertaken to investigate how many KRs would be prevented at different levels of pain improvement, a major target of osteoarthritis (OA) trials.We used data from the Osteoarthritis Initiative (OAI) to emulate a trial of knee pain interventions on KR risk changes. We modeled hypothetical 1-, 2- or 3-unit reductions of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale whenever a person reported a pain score of ≥5 (of 20) in an affected knee at any clinic visit. We used causal inference-based targeted learning to estimate treatment effects for hypothesized pain intervention strategies adjusted for time-dependent confounding. Sensitivity analyses assessed interventions at WOMAC pain scores of ≥4 and ≥7.Of the 9,592 knees studied (n = 4,796 participants; 58.5% female; baseline age 61.2 years), 40.7% experienced WOMAC pain scores of ≥5. The estimated knee-level (reference) risk of a KR, adjusted for loss to follow-up and death, was 6.3% (95% confidence interval 5.0, 7.7%) in the OAI. Reductions of WOMAC pain scores by 1, 2, or 3 units decreased the KR risk from 6.3% to 5.8%, 5.3%, and 4.9%, respectively. Larger reductions in KR risk were achieved when interventions were applied at a WOMAC pain score of ≥4.Modest pain reductions from OA interventions would substantially reduce the number of KRs, with greater reductions achieved when pain decreased more and when interventions were introduced at lower pain levels.
Impaired regulation of MMP2/16–MLCK3 by miR-146a-5p increased susceptibility to myocardial ischaemic injury in aging mice
Authors: Ming Dong, Dishen Chen, Yanxia Zhu, Shu Yang, Santosh Kumar, Rui Zhang, Yin Zhou, Ziyi Yang, Na Zheng, Ting Zhu, Jiaqing Xiang, Yun Liu, Lin Kang, Jie Liu
Journal: Cardiovascular Research (2022)

Abstract Aims Aging impairs cardiac function and increases susceptibility to myocardial ischaemic injury. Cardiac myosin light chain kinase (MLCK3) phosphorylates cardiac myosin regulatory light chain (MLC2), controlling sarcomere organization and cardiomyocyte contraction. Dysregulation of MLCK3 and phosphorylated MLC2 (p-MLC2) contributes to heart failure after myocardial infarction (MI). We aimed at exploring how the MLCK3–p-MLC2 axis changes in aging hearts post MI and at investigating the underlying regulatory mechanisms. Methods and results We generated adult (3 months) and aged (30 months) MI mouse models to compare their cardiac performance, and then detected MLCK3 expression and MLC2 activity. Aging increased the size of MI-induced infarctions and promoted cardiac contractile dysfunction. Furthermore, MLCK3 expression and MLC2 activity increased in adult hearts after MI, but not in aged hearts. miR-146a was found consistently increased in adult and aged hearts post MI. Mechanistic analyses performed in vitro demonstrated that miR-146a-5p down-regulated matrix metalloprotease (MMP)2/16 expression in cardiomyocytes. This down-regulation in turn increased MLCK3 expression and MLC2 activity. However, miR-146a-5p failed to regulate the MMP2/16–MLCK3–p-MLC2 axis in senescent cardiomyocytes or in cardiac miR-146a conditional knockout mice, with the latter experiencing an exacerbated deterioration of cardiac function post MI. Conclusion These results suggest that an increase of MLCK3 and p-MLC2 contents through decreasing MMP2/16 by miR-146a-5p represents a compensatory mechanism that can protect cardiac contractile function after MI. Aging impairs this miR-146a-5p-regulated MMP2/16–MLCK3–p-MLC2 contractile axis, leading to compromised contractile function and increased susceptibility to heart failure.
Deep Learning for Nuchal Translucency–Based Screening for Fetal Trisomy 21
Authors: Tuangsit Wataganara
Journal: JAMA Network Open (2022)

Liwen Zhang, PhD; Di Dong, PhD; Yongqing Sun, MD; Chaoen Hu, MS; Congxin Sun, BD; Qingqing Wu, MD; Jie Tian, PhD
Decreased synapse‐associated proteins are associated with the onset of epileptic memory impairment in endothelial <i>CDK5</i>‐deficient mice
Authors: Zheng‐Mao Li, Xiu‐Xiu Liu, Chen Li, Zhao‐Cong Wei, Yi Shi, Heng‐Yi Song, Xiang Chen, Yu Zhang, Jia‐Wei Li, Rui‐Fang Zhu, Ben‐Hui Hu, Wei‐Feng Ye, Da Huo, Guo‐Jun Jiang, Takuya Sasaki, Li Zhang, Feng Han, Ying‐Mei Lu
Journal: MedComm (2022)

Accumulating evidence indicates that epilepsy has a higher risk of inducing memory impairment and dementia. However, the underlying onset mechanism remains unclear. Here, we found that mice with spontaneous epilepsy induced by endothelial CDK5 deficiency exhibited hippocampal-dependent memory impairment at 6 months of age, but not at 2 months of age. Moreover, the persistent epileptic seizures induce aberrant changes in phosphorylation of CaMKII protein in the hippocampus of spontaneous epileptic mice. Using genome-wide RNA sequencing and intergenic interaction analysis of STRING, we found that in addition to epilepsy-related genes, there are changes in synaptic organization pathway node genes, such as
Enhanced neoepitope-specific immunity following neoadjuvant PD-L1 and TGF-β blockade in HPV-unrelated head and neck cancer
Authors: Jason M. Redman, Jay Friedman, Yvette Robbins, Cem Sievers, Xinping Yang, Wiem Lassoued, Andrew Sinkoe, Antonios Papanicolau-Sengos, Chyi-Chia Lee, Jennifer L. Marte, Evrim Turkbey, Wojtek Mydlarz, Arjun Joshi, Nyall R. London, Matthew Pierce, Rodney Taylor, Steven Hong, Andy Nguyen, Patrick Soon-Shiong, Jeffrey Schlom, James L. Gulley, Clint T. Allen
Journal: Journal of Clinical Investigation (2022)

BACKGROUNDHead and neck squamous cell carcinoma not associated with HPV (HPV-unrelated HNSCC) is associated with a high rate of recurrence and poor survival.METHODSWe conducted a clinical trial in 14 patients with newly diagnosed HPV-unrelated HNSCC to evaluate the safety and efficacy of neoadjuvant bintrafusp alfa, a bifunctional fusion protein that blocks programmed death ligand 1 (PD-L1) and neutralizes TGF-β.RESULTSBintrafusp alfa was well tolerated, and no treatment-associated surgical delays or complications occurred. Objective pathologic responses (PRs) were observed, and 12 of the 14 (86%) patients were alive and disease free at 1 year. Alterations in Treg infiltration and spatial distribution relative to proliferating CD8+ T cells indicated a reversal of Treg immunosuppression in the primary tumor. Detection of neoepitope-specific tumor T cell responses, but not virus-specific responses, correlated with the development of a PR. Detection of neoepitope-specific responses and PRs in tumors was not correlated with genomic features or tumor antigenicity but was associated with reduced pretreatment myeloid cell tumor infiltration. These results indicate that dual PD-L1 and TGF-β blockade can safely enhance tumor antigen-specific immunity and highlight the feasibility of multimechanism neoadjuvant immunotherapy for patients with HPV-unrelated HNSCC.CONCLUSIONOur studies provide insight into the ability of neoadjuvant immunotherapy to induce polyclonal neoadjuvant-specific T cell responses in tumors and suggest that features of the tumor microenvironment, such as myeloid cell infiltration, may be a major determinant of enhanced antitumor immunity following such treatment.TRIAL REGISTRATIONClinicalTrials.gov NCT04247282.FUNDINGThis work was funded by the Center for Cancer Research, the NCI, and the Intramural Research Program of the NIDCD, NIH. Bintrafusp alfa was provided by the health care business of Merck KGaA (Darmstadt, Germany), through a Cooperative Research and Development Agreement with the NCI. Additional funding was provided by ImmunityBio through a Cooperative Research and Development Agreement with the NIDCD.
Recent Use of Non–Vitamin K Antagonist Oral Anticoagulants and Intracranial Hemorrhage Among Patients With Acute Ischemic Stroke Treated With Alteplase—Reply
Authors: Wayneho Kam, Ying Xian
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Competency-Based Alternative Training Pathway in Cardiovascular Disease and Clinical Cardiac Electrophysiology
Authors: Lisa A. Mendes, Gaby Weissman, Katie Berlacher, Julie B. Damp, Jose A. Joglar, Judith Mackall, Chittur A. Sivaram, Ada C. Stefanescu Schmidt, Eric S. Williams, James A. Arrighi
Journal: Journal of the American College of Cardiology (2022)
Carotid Sinus Massage Is the Message
Authors: Mazen M. Kawji
Journal: JAMA Internal Medicine (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Overlooking a More Typical Culprit
Authors: Xiaohong Chen, Ting-Ting Li, Chuan-Hai Zhang
Journal: JAMA Internal Medicine (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Novel Radiomic Measurements of Tumor-Associated Vasculature Morphology on Clinical Imaging as a Biomarker of Treatment Response in Multiple Cancers
Authors: Nathaniel Braman, Prateek Prasanna, Kaustav Bera, Mehdi Alilou, Mohammadhadi Khorrami, Patrick Leo, Maryam Etesami, Manasa Vulchi, Paulette Turk, Amit Gupta, Prantesh Jain, Pingfu Fu, Nathan Pennell, Vamsidhar Velcheti, Jame Abraham, Donna Plecha, Anant Madabhushi
Journal: Clinical Cancer Research (2022)

Purpose: Tumor-associated vasculature differs from healthy blood vessels by its chaotic architecture and twistedness, which promotes treatment resistance. Measurable differences in these attributes may help stratify patients by likely benefit of systemic therapy (e.g. chemotherapy). In this work, we present a new category of radiomic biomarkers called quantitative tumor-associated vasculature (QuanTAV) features, and demonstrate their ability to predict response and survival across multiple cancers, imaging modalities, and treatment regimens. Experimental Design: We segmented tumor vessels and computed mathematical measurements of twistedness and organization on routine pre-treatment radiology (CT or contrast-enhanced MRI) from 558 patients, who received one of four first-line chemotherapy-based therapeutic intervention strategies for breast (n=371) or non-small cell lung cancer (NSCLC, n=187). Results: Across 4 chemotherapy-based treatment strategies, classifiers of QuanTAV measurements significantly (p<.05) predicted response in held out testing cohorts alone (AUC=0.63-0.71) and increased AUC by 0.06-0.12 when added to models of significant clinical variables alone. QuanTAV risk scores were prognostic of recurrence free survival in treatment cohorts chemotherapy for breast cancer (p=0.002, HR=1.25, 95% CI 1.08-1.44, C-index=.66) and chemoradiation for NSCLC (p=0.039, HR=1.28, 95% CI 1.01-1.62, C-index=0.66). Categorical QuanTAV risk groups were independently prognostic among all treatment groups, including NSCLC patients receiving chemotherapy (p=0.034, HR=2.29, 95% CI 1.07-4.94, C-index=0.62). Conclusions: Across these domains, we observed an association of vascular morphology on radiology with treatment outcome. Our findings suggest the potential of tumor-associated vasculature shape and structure as a prognostic and predictive biomarker for multiple cancers and treatments.
My Patient Portal
Authors: Peter C. Adamson
Journal: Annals of Internal Medicine (2022)

On Being a PatientJune 2022My Patient PortalPeter C. Adamson, MDPeter C. Adamson, MDPerelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, and Sanofi, Cambridge, MassachusettsSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M22-0544 Audio Reading - “My Patient Portal” Audio. Michael A. Lacombe, MD, Annals Associate Editor, reads “My Patient Portal” by Peter C. Adamson, MD Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail The text message informing me of a new result in my patient portal arrived late Thanksgiving Day. I had been experiencing nonspecific abdominal cramping for about 4 weeks. My internist found that results of my physical examination and routine laboratory tests were normal. Because I had undergone routine colonoscopies in the past and was due for another in 2 months, she provided me with some suggestions for symptomatic relief. However, she advised that if there was no improvement, she would order an abdominopelvic CT scan. After about 1 week, suspecting I could have diverticulitis, I went ahead with the scan.... Author, Article, and Disclosure InformationAffiliations: Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, and Sanofi, Cambridge, MassachusettsCorresponding Author: Peter C. Adamson, MD, Sanofi, 450 Water Street, Cambridge, MA 02142; e-mail, peter.[email protected]com. PreviousarticleNextarticle Advertisement Audio Reading - “My Patient Portal” Audio. Michael A. Lacombe, MD, Annals Associate Editor, reads “My Patient Portal” by Peter C. Adamson, MD Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics June 2022Volume 175, Issue 6Page: 905 ePublished: 21 June 2022 Issue Published: June 2022 Copyright & PermissionsCopyright © 2022 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...